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Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A

Collins, P. W. ; Blanchette, V. S. ; Fischer, K. ; Bjorkman, S. ; Oh, M. ; Fritsch, S. ; Schroth, P. ; Spotts, G. ; Astermark, Jan LU and Ewenstein, B. (2009) In Journal of Thrombosis and Haemostasis 7(3). p.413-420
Abstract
Background: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level < 1 IU dL(-1). Studies to date, however, have not demonstrated a strong link between FVIII level and the bleeding rate. Objectives: To assess the effect of FVIII level on break-through bleeding in patients with severe hemophilia A on prophylaxis. Patients/methods: This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII < 1 IU dL(-1)) who were treated with prophylactic FVIII as part of clinical... (More)
Background: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level < 1 IU dL(-1). Studies to date, however, have not demonstrated a strong link between FVIII level and the bleeding rate. Objectives: To assess the effect of FVIII level on break-through bleeding in patients with severe hemophilia A on prophylaxis. Patients/methods: This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII < 1 IU dL(-1)) who were treated with prophylactic FVIII as part of clinical studies assessing pharmacokinetics, safety and efficacy of a recombinant FVIII (Advate((R))). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). Results: The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. Conclusions: These data have important implications for the management of patients with severe hemophilia. (Less)
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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pharmacokinetics, hemophilia A, bleeding, factor VIII, prophylaxis
in
Journal of Thrombosis and Haemostasis
volume
7
issue
3
pages
413 - 420
publisher
Wiley-Blackwell
external identifiers
  • wos:000263256100006
  • scopus:59849093369
ISSN
1538-7933
DOI
10.1111/j.1538-7836.2008.03270.x
language
English
LU publication?
yes
id
9a80e1f5-b08f-4f17-9c7d-9f4327350670 (old id 1374911)
date added to LUP
2016-04-01 11:48:26
date last changed
2022-05-14 05:15:17
@article{9a80e1f5-b08f-4f17-9c7d-9f4327350670,
  abstract     = {{Background: The role of prophylactic factor VIII (FVIII) to decrease hemophilic bleeding and arthropathy is well established. The rationale for this strategy is to convert patients with severe hemophilia A to a moderate clinical phenotype by reducing time spent with a FVIII level &lt; 1 IU dL(-1). Studies to date, however, have not demonstrated a strong link between FVIII level and the bleeding rate. Objectives: To assess the effect of FVIII level on break-through bleeding in patients with severe hemophilia A on prophylaxis. Patients/methods: This study analysed data from 44 patients aged 1-6 and 99 patients aged 10-65 years with severe hemophilia A (FVIII &lt; 1 IU dL(-1)) who were treated with prophylactic FVIII as part of clinical studies assessing pharmacokinetics, safety and efficacy of a recombinant FVIII (Advate((R))). Each patient had pharmacokinetic measurements and FVIII infusions recorded, and these were used to calculate time spent with a FVIII below 1, 2 and 5 IU dL(-1). Results: The data demonstrate that increasing time with a FVIII below 1 IU dL(-1) is associated with increased total bleeds and hemarthroses. Lack of adherence to the intended frequency of FVIII infusion was the most important determinant of low FVIII and increased bleeding. In children aged 1-6 years, the rate of bleeding was also influenced by FVIII half-life and clearance. Conclusions: These data have important implications for the management of patients with severe hemophilia.}},
  author       = {{Collins, P. W. and Blanchette, V. S. and Fischer, K. and Bjorkman, S. and Oh, M. and Fritsch, S. and Schroth, P. and Spotts, G. and Astermark, Jan and Ewenstein, B.}},
  issn         = {{1538-7933}},
  keywords     = {{pharmacokinetics; hemophilia A; bleeding; factor VIII; prophylaxis}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{413--420}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Thrombosis and Haemostasis}},
  title        = {{Break-through bleeding in relation to predicted factor VIII levels in patients receiving prophylactic treatment for severe hemophilia A}},
  url          = {{http://dx.doi.org/10.1111/j.1538-7836.2008.03270.x}},
  doi          = {{10.1111/j.1538-7836.2008.03270.x}},
  volume       = {{7}},
  year         = {{2009}},
}